Antiacid compositions



Nov. 7, 1944. wl L LlPscHlTz ANTI-ACID COMPOSITION Filed Aug. 16, 1941INVENTOR Wf/P/Vf'i l'. /P5CVV/7'Z, BY Ww NJ.

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Patented Nov. 7, 1944 Werner L. Lipschitz, Pearl River,

Laboratories. Inc., a corporation ot Delaware to Lederle N. Y., assignerNew York, N. Y..

Application August 16, 1941, Serial No. 407,228

(Cl. 167-55) Y 3 Claims.

The present invention relates to pharmaceutical compositions and moreparticularly relates to improved anti-acid preparations.

There are several disadvantages accompanying the use of stronglyalkaline anti-acid compositions used heretofore for combating gastricacidity. Some of the outstanding disadvantages of such preparations arethat they irritate mucous tissues, produce large quantities of carbondioxide gas, and reduce the acidity of the gastric juices to such anextent that normal digestion processes do not proceed properly.

In accordance with the present invention I have discovered a class ofanti-acid compositions which eliminate to a very great extent thedisadvantages of the prior art compositions. Briefly, my improvedpreparations comprise a mixture o f casein salts of polyvalent cationswith an insoluble carbonate oi' a polyvalent cation. My preferredcompositions are those comprised of al mixture of a casein salt of abivalent cation with an insoluble V carbonate of a bivalent cation.Caseinates suitable for use in producing my composition comprise thosesuch as calcium caseinate, strontium caseinate, magnesium caseinate, andthe like, calcium being preferred because of its cheapness and readyavailability. Suitable polyvalent carbonates include calcium carbonate,magnesium carbonate, strontium carbonate, bismuth subcarbonate, and thelike. It is an advantage of the present invention that my anti-acidcompositions, comprising mixturesv of protein salts of bivalent cationscombined with polyvalent carbonates, are anti-acids having a prolongedneutralization effect and have a protective action on the mucosa. It isa further advantage that the quantity of carbon dioxide gas liberated byvthe neutralization reaction is less than the quantity that would beliberated by neutralizing an equivalent amount of the correspondingcarbonate alone. It 'is also an advantage that the pH of the gastriciiuids is not raised materially beyond that at which normal digestionwill take place. It is an advantage that after` digestion of the caseinsalt by pepsin, the basic portions of the protein molecule are set freeand there is an increased neutralization effect produced.

The protein salts ployed in my compositions any suitable method so longcient purity for internal administration. A suitable method forpreparing calcium caselnate, for example, having a high degree of purityis as follows: y

Fifteen parts 'of casein (Hammarsten) Iwere may be prepared by as theyare of suiii-` by help of cc. distilled lwater in-a glass mortardissolved in 200 parts of a solutionl of 0.63% sodium bicarbonate. Thesolution of casein in sodium bicarbonate is saturated with carbondioxide gas and stirred while adding 100 parts of 10% calcium chloride.The liquid portion is decanted oil and the residue washed several timeswith distilled water and decanted. The residue is lthen dried andresults in thevproduction of a yellow powder. The calcium caseinate maythen be mixed with calcium carbonate to produce an anti-acidcomposition, or with the various other polyvalent carbonates mentionedheretofore.

In some instances it may be desirable to produce the protein salts ofbivalent cations by reacting casein with a large amount of a bivalentcarbonate to result in the production of a product made up of a mixtureof the bivalent caseinate and the bivalent carbonate, as follows:

Five gramscasein (Hammarsten) and one and a half grams CaCOi wereadmixed with cc. distilled water in ya mortar with pestle thoroughlyuntil carbon dioxide wasy gone and a homogeneous mass obtained. hours at70 C.

Five grams casein (Hammarsten) and 1.476 grams of SrCOs were slowlyandcarefully mixed for.24 hours in an oven. The dried mass then waspowdered carefully for several days.

1.383 grams of Mgcol+3rr2o were'admired with five grams casein`(Haminarsten) by help of 35 cc. distilled water slowly in a glassmortar of the bivalent cations em with pestle. After most of the carbondioxide was liberated, the mixture was dried in a Pyrex beaker in anoven at 60 C.

5.2 grams bismuth sub-carbonatev (m. w. 519 containing 8.5% Cor-1l mol)were carefully mixed with five grams casein and 60 cc. distilled water,then transferred to a Pyrexv beaker and dried in a water bath of C.

A number of experiments were carried out inv order to illustrate theneutralization effect of various combinations of casein salts ofbivalent cations combined with a polyvalent carbonate. In performingthese exv periments electrical titrations were made to de- 1- terminethe hydrochloric of the individual acid neutralizing eilect produced,and these results compared with those obtained by similar experimentscarried out on the various mixtures. The titrations were .carried out bymethods well known in the art and the carbon dioxide retention was de-This, then, was dried for 24 and kept in a desiccatorl of the mixturesof proteins components in the mixture, the time of the neutralization,the quantity of carbon dioxide gas termined by means of the Warburgmethod which is also well known in the art. The results of theseexperiments are tabulated in the following table: v

tion salt of casein and an insoluble carbonate of a polyvalent cation.It should be understood, however. that other substances may beincorporated therein without materially altering In the foregoing tableit is clearly shown'that the mixture of'calcium caseinate and calciumcarbonate requires a greater amount of HC1 in order to obtain a solutionhaving a pH of 2.5 than would be expected from the amounts ofhydrochloric acid required when the individual ingredients are treatedseparate. It is further noted that in the reaction between calciumcarbonate and hydrochloric acid that there is no retention whatever ofcarbon dioxide, in other words the entire amount of CO2 produced in theneutralization reaction is given oi. In the case of the mixture ofcalcium carbonate and calcium caseinate of the carbon dioxide isretained, or a volume oi carbon dioxide liberated is only aboutthree-fourths of that liberated when calcium carbonate alone isneutralized.

KIt is also noted that there is an elapse oi about 20 minutes in thereaction between hydrochloric acid and the mixture of calcium caseinateand calcium carbonate before the pH of the solution has reached 2.5.When calcium carbonate alone is employed elapse of time is only 4-5minutes. This is an important factor in anti-acid compositions becausethe neutralization eiect is a prolonged one which means that thealkaline reagent is present and, hence,` available for neutralizingfurther quantities of HCl as it is liberated by the system. Furthermore,when the neutralization is rapid and the pH of the gastric juices risesabove 4.0, normal digestion processes are retarded. v

When calcium carbonate alone is employed, it is noted that there is noincrease of the pH value after digestion with pepsin, whereas in thecase Und 00| retention Min. ela g,N, ,-Ht mmtt' m3 p i ar w renc v pHvessels at 37 C. in mixtures Ism?! Preparation ft2 Wmwfe @man Per i m01am no1 W 92pm 4 s r2.5 Mol carbonate 0. con- 5 37 C',

HCl were tinuous added stirring) 334 Ca cucinato. 3.0 8. 0 CIO i 1 m.mol 20 20.3 i in. mol CsC0n+334 l 24 20 0.004 m. mol CaCO; 12.8 13 0.604m. mol. CaC Ori-351.4 mg. Cs cucinato powder i9 21 8:00a 0.85 m m 13 i3.3 0.66 m. mol. BrC0i+334 mg Br caseiuate 20 MgCO; 0.7 m. mol- 15 0.7 m.mol. MgOOa-Hl? mg.. Mg caseinste- 2i zi. 4 Sr00| 0.53 m. moli-340.5 mg.Ca caseinate lo 18.5

M3001 0.6 m. moli-348 mg. Ca caselnato 18. 6 21 the improved effects ofmy composition. Among the substances that may be incorporated thereinare those such as magnesium trisilcate, aluminum hydroxide, kaolin,cnarcoal, pectin, or various other substances which might have aprolonged neutralization eilect, adsorbent effect or act as a protectiveto mucous linings.

My compositions may be in the form oi bulk powders or in the form oftablets. When they are in the form of tablets, suitable fillers andbinders may be incorporated therein.

The proportions of the essential ingredients in my composition may bevaried to a considerable extent, the maximum anti-acid eiects I believe,however, are obtained when the proportions are approximately equivalentto those produced by reacting iive parts of casein with one of themixture of calcium carbonate and calcium caseinate there is an increaseof about .75;

and a half parts of calcium carbonate which will give a compositioncontaining about 5 parts of calcium caseinate and about one part ofcalcium carbonate. When other polyvalent caseinates and other polyvalentcarbonates are employed the proportions may be adjusted on the basis ofmolecular weights so that they correspond roughly to those present inthe calcium carbonate and calcium caseinate mixture. In the compositionsthe casein salt of one polyvalent cation may be mixed with an insolublecarbonate of the same or a. different polyvalent cation. Similarly,mixtures of the various polyvalent caseinates or polyvalentcarbonates'may be employed.

What I claim is:

1. An anti-acid composition comprising Ia mixture containing about onepart of calcium carbonate and about five parts of calcium caseinate.

2. An anti-acid composition comprising a mixture of which the essentialcomponents thereof consist of a major proportion of calcium caseinateand a minor proportion of calcium carbonate.

3. An anti-acid composition comprising a mixture of calcium carbonate,calcium caseinate and aluminum hydroxide gel, the essential componentsof said mixture consisting of a major proportion of calcium caseinateand a minor WERNER L. LIPSCHITZ.

